Project Summary Environmental factors are known to play a major role in driving worldwide cancer burden. In particular, epidemiological evidence strongly links constituents of outdoor air pollution, such as particulate matter and benzene, to increased lung cancer incidence and mortality. Nonetheless, when the International Agency for Research on Cancer recently classified outdoor air pollution as a known human carcinogen, it acknowledged that spatial and temporal variation in air pollution makes generalization across diverse exposure sources challenging. This is a barrier to determining patterns of exposure and to designing strategies for mitigation. Moreover, increasing energy consumption and anthropogenic emissions directly contribute to airborne pollution. This is of particular concern in rapidly industrializing urban areas, such as the Yangtze River delta region surrounding Shanghai, where essentially all residents experience unsafe air pollution levels on a daily basis. Thus, scientific efforts to address this problem must meet a dual challenge: impel fundamental change to monolithic industrial and energy sectors, while simultaneously providing effective strategies for risk mitigation at the individual level in the interim. Dating from the late 1980s to the present, we have conducted numerous cohort and clinical studies in Qidong, which lies opposite Shanghai on the northern banks of the Yangtze. As a result, we hold a large archive of samples obtained from Qidong residents between 1989 and 2018, providing us with a truly unique, three-decade biorepository in which to utilize adductomic approaches to interrogate air pollution exposures. Using a novel adductomic method, in participants recruited from Qidong over three decades (1989- 2018), Aim 1 will characterize air pollutant adducts to the Cys34 nucleophilic hotspot of serum albumin. We hypothesize that adduct biomarkers of airborne pollutant internal dose will increase from 1989 to 2018. Results from this Aim will, for the first time, provide data on airborne pollutant internal dose across several decades, in a region experiencing rapid industrialization and rising lung cancer risk. In Aim 2, we will apply our Cys34 adductomics method to our previous 12-week chemoprevention trial, conducted in Qidong in 2011, in which we demonstrated the efficacy of a broccoli-based intervention in protection against airborne pollutant exposure. Based on our previous findings and preliminary data, we hypothesize that broccoli treatment will reduce adducts of several airborne pollutants ? particularly benzene, a known human carcinogen. Results from Aim 2 will strengthen the tools available to monitor and mitigate air pollution exposures. Leveraging the value of our biorepository, the work proposed is uniquely positioned and has significant potential to advance the cancer prevention field. The proposed studies would uniquely provide an objective assessment of air pollutant internal dose over a three-decade period of rapid economic development and rising cancer risk, while also advancing evidence on an economical strategy for secondary cancer prevention.